Non alcoholic fatty liver dis. accumulation of macro vesicular fat in hepatocytes up to 40% of liver weight. Terminology: hepatic steatosis in obese adults half century ago Findings in liver histology 1979 similar to Alcoholic liver dis. ( NAFLD ) NASH 1980
Hepatic steatosis: Primary: Obesity - ins resistance Secondary : drugs – Toxin metabolic – etc. Epidemiology: FL in 2/6% school age children in Japan. FL in 9% of autopsies in 2-19 yrs old.
Pathophysiology: In fed state ins and parasympatic system lipid accumulation in liver and adipose tissue In fasting glucagon and sympatic system FFA as brain and muscle fuel. Starvation TPN DM steroids FFA, but not oxidation in liver steatosis
Obesity DMhyperlipemia Insulin resistance FFA in liver Steatosis NAFLD Oxidative stress Lipid peroxidation Genetic glutatione ATP Inflam. Cytokines Inflam. Necrosis fibrosis NASH
8-10% of NAFLD have DM Ins resistance glucose transport and metabolism in adipocytes and skeletal muscle lipolysis circulating FFA
Diagnosis: usually asymptomatic ALT 90% NAFLD children are obese acanthosisnigricans in 30-50% vague abd. pain in 30% hepatomegaly in 40-50%
DD: infection : HCV immunologic : AIH celiac IBD DM 1 medication : Amiodarone glucocorticoids antiretroviral tetracyclin L- Asparginase colchicin valproic acid
Metabolic :abetalipoproteinemia α1 AT Def. galactosemia tyrosinemia fruct. Int. GSD TG Reye homocystinuria wilson mitochondrial dis.
Nutritional : PEM EFA starvation obesity jejunoileal bypass TPN Toxins: ethanol
Pathology: for 1) definitive diagnosis of NAFLD 2) discrimination of NASH from milder forms of FL 3) diagnosis of other cases like AIH 4)in adults with suspected NAFLD DM2 age>40yrs
NASH NAFLD: Macrovesicular steatosis Perisinosoidal fibrosis Balloon degeneration Lobular inflammation Mallory hyaline Megamitochondria Brunt criteria: steatosis (0-3) lobular inflammation (0-3) ballooning (0-2)
Progression rate to cirrhosis is unknown • NASH induced CLD are suseptible to HCC. • Advanced fibrosis is present at the time of diagnosis in 5-10% of children with NAFLD
ALT - > 1/7 - GGT - TG NL FBS - fasting insulin - TNFα- Adiponectin
The minimum warkup : FBS insuline lipids TFT?
Imaging : sonography when the liver fat is >30% CT without contrast MRI ( Ideal )
Treatment : control of weight change in life style diet exercise taurine Vit E ursobil metformin
Metabolic Syndrome (Syndrome X) Metabolic Syndrome(Syndrome X) • 3 or more of the following: • 1.Abdominal obesity (waist > 40” for men and 34.5” for women) • 2.Triglyceride level >150 mg/dL • 3.HDL <40 mg/dL for men and <50 mg/dL for women • 4.Fasting blood glucose 110 mg/dL • 5.Blood pressure 130/85
NAFLD Spectrum of Hepatic Pathology Steatohepatitis Steatosis Cirrhosis Hepatocellular carcinoma